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"Some people in developing countries have expressed fears they are going to be used as guinea pigs to test vaccines that are not going to be useful in their country," said Patricia Fast, associate director of vaccine research at the National Institute of Allergy and Infectious Diseases (NIAID).

In the past two years, vaccine manufacturers have become increasingly sensitive to these concerns. Some are modifying their vaccines (most of which have been targeted at the HIV clade most common in the United States and Western Europe) to be more effective against the HIV clade present in the country where testing will occur. And several manufacturers are using vaccine clinical trials as a way to pass advanced medical technology to these countries.

A large clinical trial about to begin in Uganda, for example, will involve complex T-cell studies conducted by newly trained local technicians in a state-of-the-art immunology laboratory built there with international assistance.

A similar arrangement was negotiated between vaccine manufacturers and officials in Thailand in advance of studies scheduled to begin there this fall. Local scientists are being trained in data management, clinical trial design and vaccinology, said John G. McNeil, chief of HIV vaccine development at Walter Reed Army Institute, which helped negotiate the deal. Ultimately the agreement could lead to construction of a high-tech facility that would let Thailand buy a successful vaccine in bulk quantities at greatly reduced prices and then fill and label individual vials within its own borders.

Ultimately, of course, the ethics of international clinical testing come down to how individuals are treated. Are people told, in clear language, about the true risks and benefits of participation? Do they have a real option of declining without fear of punishment? Or, more difficult: Is it acceptable for vaccine developers to offer rewards to volunteers?

"There are a lot of questions in the ethics literature as to whether inducements are appropriate or undue," said Christine Grady, acting chief of bioethics at the National Institutes of Health's clinical research center. Also in dispute, she said, is whether the answers to these questions are the same in all places; whether there is, in essence, a universal ethic, or whether it may vary from country to country, with perhaps greater risks or stronger inducements acceptable in countries where the epidemic is spreading fastest.

If the rules of engagement for a clinical trial are indeed variable from country to country, then any effort to impose, for example, U.S. standards of informed consent might amount to "ethical imperialism." On the other hand, some fear that this sort of thinking may be used as an excuse to afford fewer protections to volunteers in developing countries.

To make sure that the rights of individuals are not abrogated during the testing of an AIDS vaccine, several international, national and — perhaps most important — grass-roots community groups in several countries are creating educational materials and workshops for residents, community leaders and members of the local media, to help them understand AIDS vaccine research.

"This is going to be a very long-term effort," said Fast of NIAID, speaking of both the scientific and humanitarian challenges of bringing an AIDS vaccine to the developing world. "But I think it's going to be successful."

And, as many scientists will concede, that optimism was not present a few years ago.